A spoonful of cholesterol helps the neurons to grow

One popular misconception about the brain is that it stops growing in adulthood.

Neurons make up the brain and central nervous system. Disease can destroy neurons much faster than they can be replaced.

It’s true that a person has a finite amount of brain cells – and that activities such as drinking, contact sports and watching reality television only serve to lower that number – but the brain does continue to make new neurons as a person ages. Conditions such as Parkinson’s disease, however, can wreak more destruction than can be naturally regenerated.

Now an international team of researchers have identified compounds that play an important role in promoting the growth and survival of new neurons. Scientists already understood what engine drove neural stem cell replication, but until now did not know what key started the process.

The team's findings were posted online Dec. 23 in advance of print publication in the journal Nature Chemical Biology. The researchers said in their paper that their work identifies “an entirely new class of highly selective and cell type-specific regulators of neurogenesis and neuronal survival.”

Now for some background: Medical experts split the brain into three basic areas – forebrain, midbrain and hindbrain. The midbrain is responsible for sight, hearing, motor control, sleeping and waking, alertness and regulating body temperature. Receptors are protein molecules that read sections of DNA to produce what is coded in those sections, such as new neurons. Ligands are proteins that can turn a receptor on and off.

Researchers find key to turn on production of new neurons.

Scientists had already identified that Liver X receptors need to be activated in the midbrain in order to generate new neurons, but up until now, they had not been able to identify the specific protein ligand that turned on the receptors.

The Liver X receptor is so named because it is most active in the liver, though it is found in many organs including the brain. And even in the brain, the Liver X receptor is activated by two cholesterol-related compounds, cholic acid and a type of oxysterol known as 24(S),25-epoxycholesterol.

Those compounds switch on the formation of neurons (a process known as neurogenesis) in the midbrain, with cholic acid especially helpful in generating new neurons related to motor function. The addition of oxysterol to replicating embryonic stem cells nudges more cells to differentiate into neurons.

The researchers say in their published study that the discovery of the specific cholic acid and oxysterol ligands may “contribute to the development of cell replacement and regenerative therapies for Parkinson’s disease.”

Members of the international team included postdoctoral fellows from City of Hope and researchers from the Karolinska Institute, and Center for Biosciences, in Stockholm, Sweden; Swansea University in Swansea, U.K.; Waters UK Ltd in Manchester, U.K.; and the University of Houston in Houston, Texas.